Advanced Healthcare Materials最新文献

The development of small-caliber tissue-engineered vascular grafts (sTEVGs) presents several challenges, including achieving balanced endothelialization, facilitating smooth muscle cell infiltration, preventing leakage, and ensuring anti-thrombogenic properties, while maintaining mechanical strength sufficient to withstand physiological pressures, surgical handling, and suturing. Here, we present a multi-layered polycaprolactone (PCL)-based sTEVG using a combination of electrospinning and 4-axis printing, providing precise control over scaffold porosity, fiber alignment, and tunable mechanical properties. To improve biocompatibility and hemocompatibility, the PCL nanofibers were functionalized with sulfated polysaccharides purified from the marine invertebrate Holothuria tubulosa, which significantly enhanced endothelialization and provided strong anti-thrombogenic properties. The inner layer of tightly aligned electrospun nanofibers supported rapid formation of a mature endothelium, while preventing graft leakage even at supraphysiological pressure (>1100 mmHg). The middle layers, combining circumferential electrospun nanofibers and 4-axis printed microfibers, increased scaffold porosity, and promoted adhesion, orientation and infiltration of human coronary artery smooth muscle cells (HCASMCs), facilitating functional tunica media formation. The outer layer of randomly oriented electrospun nanofibers contributed significantly to the mechanical properties of the graft, namely elasticity, toughness, burst pressure, and resistance to physiological vessel pressures, thus mimicking the tunica adventitia. The customizable four-layered graft integrates structural and biological cues to address key limitations of sTEVGs, representing a valuableoff-the-shelf alternative to autologous grafts.

Dynamic mechanical stimulation plays an important role in determining the function and health of cells and tissues, and it is therefore highly relevant to study the real-time response of cells to time-dependent forces. We introduce a platform for providing controllable dynamic mechanical stimulation to single cells, suitable for investigating large cell populations and enabling live cell imaging, and we present proof-of-principle experiments that demonstrate the platform's capabilities. Cells are cultured on a hydrogel surface with magnetic artificial cilia made from a magnetic elastomer using a tailored micromolding process. The cilia are actuated with an electromagnet integrated with an in-incubator fluorescent microscope. We show that cells attach to the cilia and exhibit widely different morphologies than cells on flat surfaces. Cellular forces involved can be estimated by measuring cilia deflection. We demonstrate that cells can be exposed to continuous dynamic forces by cilia actuation and that their response can be monitored by real-time observation of Yes-Associated Protein (YAP). These experiments indicate rare events of mechanotransduction due to cilia actuation, but the low response prohibits drawing final conclusions about the biological response. Our artificial cilia-based platform offers new opportunities for studying mechanical cell stimulation in real time and understanding dynamic mechanotransduction.

Nanozymes hold significant promise for periodontitis treatment, owing to their high catalytic efficiency, multi-enzyme activity, robust stability, and low cost. However, the need for repeated administration and the complex oral environment present challenges in balancing biosafety and efficiency. Herein, we develop a ligand-modulated manganese ferrite nanozyme hydrogel (MFZ@PG) with balanced antioxidant activity and biocompatibility for periodontitis treatment through ZBP1/β-catenin signaling. MFZ@PG is synthesized by encapsulating zwitterionic dopamine sulfonate-modified manganese ferrite nanoparticles within a gel matrix composed of polyvinyl alcohol, gelatin, and borax. The resulting hydrogel demonstrates potent antioxidant capacity, attributed to the innate nanozyme activity of manganese ferrite and the introduced catechol groups, as well as robust adhesiveness due to multiple chemical interactions between borax and polyvinyl alcohol. In vitro experiments demonstrate that MFZ@PG effectively protects MC3T3-E1 cells from H₂O₂-induced impairment of proliferation, migration, and osteogenic differentiation. In vivo experiments demonstrate that MFZ@PG significantly promotes alveolar bone regeneration and suppresses bone resorption. Furthermore, transcriptomic analysis indicates that the therapeutic mechanism of MFZ@PG is achieved through the activation of the ZBP1/β-catenin positive feedback loop. Histopathological and blood biochemical analyses demonstrate the good biocompatibility of MFZ@PG. This study presents a safe and efficient therapeutic strategy for periodontitis with high translational potential.

Refractory wounds caused by multidrug-resistant (MDR) bacterial infections are characterized by biofilm formation, persistent inflammation, and impaired angiogenesis, requiring stage-specific therapeutic strategies. Herein, we propose a three-in-one multifunctional metal-organic gel-encapsulated microneedle (Cu-MOG MN) with integrated antibacterial, anti-inflammatory, and pro-angiogenic capabilities for the programmed treatment of infected wound. Cu-MOG is constructed via facile coordination and self-assembly between naturally antioxidant phytic acid (PA) and essential trace element copper, and exhibits well-defined pH-responsive multienzyme activities. During the early stage of bacterial infection, Cu-MOG activates superoxide dismutase-peroxidase (SOD-POD) cascade to generate localized reactive oxygen species (ROS), enabling efficient bacterial eradication and biofilm disruption. As the wound microenvironment transitions to neutral inflammatory conditions, the catalytic profile shifts to SOD-glutathione peroxidase (GPx) activity, scavenging excess ROS and alleviating oxidative stress. In addition, Cu-MOG exerts potent immunomodulatory effects by promoting macrophage polarization toward the pro-regenerative M2 phenotype, while simultaneously enhancing collagen deposition, angiogenesis, and cell migration to accelerate wound healing. Collectively, the Cu-MOG MN system achieves a comprehensive therapeutic cascade through synergistic deep tissue penetration, pH-responsive antibacterial/anti-inflammatory actions, and pro-regenerative stimulation of collagen deposition/angiogenesis, showing great potential for precise, dynamic and adaptive treatment of refractory wounds.

Rotator cuff tears (RCT) are one of the most common causes of shoulder joint pain and mobility disorders affecting the health of middle-aged and elderly patients. Although the arthroscopic repair can effectively suture the torn rotator cuff, the retear rate is still high, especially for patients with osteoporosis. Excessive oxidative stress, uncontrolled inflammatory infiltration Bone mass reduction, muscle atrophy, and fatty infiltration would gradually aggravate during the development of RCT, which would seriously hinder the effective repair of the repaired rotator cuff after arthroscopic surgery. Herein, a novel nanozyme-based drug delivery system Nb₂C@Mg-MOF/Pluronic F127 (NMP) consisting of niobium carbide (Nb₂C), magnesium metal-organic framework (Mg-MOF), and a temperature-sensitive hydrogel (Pluronic F127) was developed for effective regulation of inflammation and orderly regeneration of various tissues from bone to muscle. The in vitro and in vivo studies have shown that NM (Nb₂C@Mg-MOF) has excellent anti-inflammatory properties. It could actively promote various tissue regeneration, including osteogenesis, inhibition of osteoclastogenesis, myogenesis, inhibit fatty infiltration and angiogenesis. This nanozyme-based drug delivery system plays an effective role in promoting healing in the complex repair process of rotator cuff tears with osteoporosis, which would provide new insights and a promising strategy for treating of osteoporotic rotator cuff tears.

Nano-based drug delivery systems often encounter challenges in insufficient tumor cell internalization, particularly in deep cells, due to dense tumor stroma, which limits drug delivery efficiency and antitumor efficacy. Here we present a smart nanoplatform (Trans-btND) with an onion-like multilayered structure, comprising a negatively charged heparin outer layer, a hyaluronidase (HAase) sublayer, and a positively charged reactive oxygen species (ROS)-responsive drug-loaded core. This design enables a triple-targeting strategy for effective tumor cell internalization: (i) heparin-mediated active targeting, driven by the affinity between heparin and overexpressed heparanase, promotes Trans-btND accumulation at tumor sites; (ii) charge-reversal-triggered tumor cell targeting, induced by the sequential degradation of heparin and HAase layers, facilitates cellular uptake via electrostatic interactions; (iii) ROS-activatable targeting, initiated by elevated intracellular ROS levels, enables precise cytosolic drug release. Notably, during the process, Trans-btND undergoes stepwise size reduction, intracellular transcytosis, and HAase-mediated stromal degradation, thereby promoting deeper tumor penetration. Therefore, Trans-btND with enhanced tumor targeting and stroma penetration can significantly augment delivery efficiency and amplify antitumor potency, providing a promising strategy for cancer therapy.

Bacterial infection remains a primary cause of delayed wound healing. It is one of the leading causes of post-surgical hospital readmission and is a major burden on global health systems. In light of the growing threat of antibiotic resistance, improving efficacy of traditional antimicrobials, such as the broad‑spectrum oxidizing biocide hydrogen peroxide, is of growing importance. In particular, solid peroxy-compounds can offer prolonged action and sustained delivery of both oxygen and reactive oxygen species, offering both infection control and microenvironmental modulation. This review presents the current progress on antimicrobial dressings, comprehensively covering the application of solid peroxide-releasing compounds in the treatment of infected wounds for antimicrobial control and acceleration of wound healing. Calcium peroxide (CaO₂) loaded biomaterials are found to be the most studied solid peroxide in the literature (90%; 30 studies), and the average improvement in healing of these reports was 26 ± 14%. However, biomaterial formulations are often complex with multiple ingredients, and an analysis of 17 studies that included peroxide-free but otherwise complete formulations identified that the improvements in wound healing attributable to peroxide loading itself were significant, P < 0.05, in 8 of 17 studies. Additionally, infected wound healing, the potential biological roles of metal ions, strategies to control ROS/O₂ release, and the translational outlook/market readiness of peroxide materials are discussed.

Noninvasive wearable stimulation-acquisition integrated brain-computer interfaces (BCIs) have significant application value in neurological rehabilitation and health monitoring. However, their widespread adoption depends on the development of long-term, stable dry/semi-dry electrodes and lightweight hardware. In this study, a sodium-doped vertical graphene (Na-VG) electrode that utilized sweat and tissue fluids as electrolytes was developed. When applied with ultrapure water, an extremely low electrode-skin impedance of 4.22 ± 0.50 kΩ was detected at 10 Hz. The 20-channel EEG cap assembled with the Na-VG electrodes maintained a high α-rhythm response of 5.06-14.22 dB in the signal-to-noise ratio of whole-brain EEG signals during a 36-day stability evaluation. Furthermore, a wearable Na-VG headband BCI combining sound-light stimulation and EEG acquisition was developed. Healthy individuals wearing this system, under the coordinated intervention of 40 Hz differential-frequency sound stimulation and 10 Hz light stimulation, showed changes in the frequency and amplitude of the α-rhythm. This improvement increased the proportion of moderate-levels of the vigilance index, neural activity, heart rate, emotion, and arousal index to 84-100%, with a precision of 98.73%. These results provide novel long-term, lightweight strategies and matching software and hardware for the monitoring and noninvasive intervention of emotional and cognitive-related diseases.

Essential metal ions such as copper and iron ions are promising tumor therapeutic targets with the emerging of cuproptosis and ferroptosis. To effectively induce cuproptosis and ferroptosis in tumor cells, copper-selenium-naphthazarin nanoparticles (CSN NPs) were rationally fabricated through the modification of ultrasmall Cu_{2- x}Se nanoparticles with naphthazarin. These nanoparticles can disrupt copper homeostasis in glioblastoma (GBM) cells to simultaneously activate cuproptosis/ferroptosis pathways and significantly enhance GBM therapy. Following surgical resection, hydrogel-mediated sustainable release of CSN NPs within the cavity resulted in the accumulation of copper ions in tumor cells, leading to aggregation of mitochondrial lipoylated proteins and iron-sulfur cluster protein loss, thereby triggering cuproptosis. Concurrently, CSN NPs triggered ferroptosis through ROS accumulation, GSH depletion, and GPX4 downregulation, due to the joint effects of the Fenton-like property of Cu_{2 - x}Se nanoparticles, the Michael reaction between naphthazarin with GSH, and the reduction of Cu²⁺ by GSH. The synergistic cuproptosis/ferroptosis induced robust immunogenic cell death (ICD) and remodeled the tumor immuno-microenvironment through enhanced infiltration of CD8⁺ and CD4⁺ T cells. The median survival time of treated GBM mice was increased by 1.9-fold compared to the untreated GBM-bearing mice. Our findings demonstrate a promising strategy of coupling cuproptosis-ferroptosis with immunotherapy through modulation of essential metal ions, presenting an innovative paradigm for GBM postoperative treatment.

Portal hypertension (PHT), a life-threatening complication of chronic liver disease, is driven by increased hepatic vascular resistance, with liver sinusoidal endothelial cell (LSEC) dysfunction and impaired nitric oxide (NO) signaling as key contributors. This study synthesized spermidine-based carbon quantum dots (ST-CQDs) and investigated their therapeutic effects on PHT. ST-CQDs (average size 2.12 nm) exhibited good biocompatibility and effectively induced NO production in human immortalized LSECs (hiLSECs) by upregulating endothelial NO synthase (eNOS). In BDL and CCl₄-induced PHT rat models, intravenous ST-CQDs reduced portal pressure by decreasing intrahepatic vascular resistance, reversed LSEC capillarization, inhibited hepatic stellate cell activation and liver fibrosis, and alleviated liver inflammation-without altering systemic hemodynamics or causing organ toxicity. In vitro, ST-CQDs reversed lipopolysaccharide-induced LSEC dysfunction by restoring eNOS expression and NO release. These findings demonstrate ST-CQDs as a potential therapeutic agent for PHT via targeting LSEC-derived NO signaling.